The specific objective of our research is to establish the biochemical mechanisms involved in the degradation of DNA by certain antitumor agents. We propose to study the mechanism of action of camptothecin and VP-16-213 in the degradation of cellular DNA and the relationship between inhibition of DNA synthesis and DNA degradation by these drugs. The products generated from the degradation of DNA by bleomycin and Fe(II) and the interaction of the Fe(II)-bleomycin complex with DNA will be investigated. Emphasis will be placed on the possible involvement of metal ions in the fragmentation of DNA. Research on drug-dependent degradation of DNA will be done with various isolated DNAs, intact HeLa cells, adenovirus-infected HeLa cells and SV40-infected BSC-1 cells.